Stimulation of microsomal prostaglandin synthesis by a blood plasma constituent which augments autoregulation and maintenance of vascular tone in isolated rabbit hearts.

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Abstract
Infusion of small amounts of plasma (1-2%) into isolated hearts perfused with Tyrode''s solution causes vasoconstriction and augments regulation of coronary flow in response to changes in perfusion pressure (autoregulation). When plasma infusion is stopped, the vasoconstrictor effect dissipates within 5 min, but the autoregulatory response remains for about 15 min. Thus the plasma-augmented autoregulatory response is not dependent on plasma-induced vasoconstriction. Indomethacin (10 .mu.g/ml), an inhibitor of prostaglandin synthetase, causes coronary vasodilation and also abolishes the lingering autoregulatory response. These effects of indomethacin are counteracted by the addition of 1.5% plasma to the perfusate. Purification procedures led to the extraction of an active material from plasma which migrates as a single substance in TLC. This substance causes coronary vasoconstriction, augments autoregulation and counteracts the effects of indomethacin in isolated rabbit hearts as effectively as plasma. The purified vasoactive substance stimulates a 2-fold increase in cardiac microsomal prostaglandin synthesis and a 5-fold increase using renal microsomal preparations. This substance counteracts indomethacin-induced inhibition of prostaglandin synthesis in microsomal preparations. These results provide convincing evidence that the effects of this plasma constituent on the coronary vasculature are mediated by stimulation of prostaglandin synthesis. Prostaglandin synthesis is probably important in both the maintenance of coronary vascular tone and the autoregulatory response in isolated rabbit hearts.